We propose to investigate the use of artificial lipid bilayer particles, liposomes, as vectos for introducing biologically active materials into tumor cells. Liposomes will be prepared from various purified and chemically-defined lipids, phospholipids and cholesterol, or from the lipids extracted from autologous organs or cells of the host. Well-defined molar ratios of positively- and negatively-charged lipids will be utilized to prepare micelles. In addition, we shall prepare glycoproteins and glycolipids from various target tissues, such as lung, mammary, liver, and prostate carcinoma. These preparations will be incorporated into the liposomes and will be tested for efficiency of fusion preferentially with the desirable target organs and with the malignant cells. Various chemotherapeutic agents such as methotrexate, Ara-C, 5-fluorouracil or new agents will be encapsulated and tested for the efficiency in delivering them with liposomes. In addition, liposomes containing the active poly-phosphorylated forms of antimetabolites will be used in efforts to circumvent drug resistance resulting from diminished intracellular net phosphorylation rates. The results of this study will contribute to the development of improved therapeutic approaches and to the possible solution of drug resistance in neoplasia.